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Temozolomide alone or in combination with capecitabine in patients with advanced neuroendocrine neoplasms: an Italian multicenter real-world analysis

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Abstract

Purpose

Temozolomide (TEM) has been reported to be active alone or in combination with capecitabine (CAP) in patients with neuroendocrine neoplasms (NENs). We retrospectively evaluated activity and toxicity of TEM-based chemotherapy in patients with advanced NENs and explored the potential correlation with clinical/biological factors.

Methods

Patients received oral TEM alone or in combination with CAP. Objective response rate (ORR) [complete response + partial response (PR)], median progression-free survival (mPFS), and toxicity were calculated. The O6-methylguanine-DNA-methyltransferase (MGMT) gene inactivation status in tumor tissue was evaluated by pyrosequencing.

Results

From September 2008 to April 2020, 170 patients (84% progressive on different therapies) were consecutively treated, 114 (67%) patients received TEM-CAP and 56 (33%) TEM alone. Primary tumor sites were: pancreas 98 (58%), gastrointestinal tract 21 (12%), lung 35 (21%), and unknown 16 (9%). The ORR was 28% for the whole population (33% for TEM-CAP and 18% for TEM as single agent). The median OS (mOS) and mPFS of the whole population were 35.6 months (32.6–48.7) and 14.7 months (10.1–18.3), respectively. There were 48% PR in the MGMT hypermethylated, mainly in pancreatic NENs. Vomiting and leukopenia were the most frequent grade 3/4 toxicity.

Conclusions

This large retrospective analysis suggested that a TEM-based chemotherapy is active in advanced, pretreated NEN patients. It generated solid hypotheses that warrant a future prospective study in a biological homogeneous NEN population and clinical setting.

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Acknowledgements

The authors thank Dr. Linda Cairns for revising English.

Author information

Authors and Affiliations

  1. Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy

    Francesca Spada & Nicola Fazio

  2. Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy

    Patrick Maisonneuve

  3. Histopathology and Molecular Diagnostics Unit, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy

    Caterina Fumagalli & Massimo Barberis

  4. Department of Oncology 2, Santa Chiara Hospital, Via Roma 67, 56100, Pisa, Italy

    Riccardo Marconcini

  5. Division of Oncology, Department of Oncology and Hematology, University Hospital, Via del Pozzo 70, 41100, Modena, Italy

    Fabio Gelsomino

  6. Medical Oncology 1, AOU Careggi Hospital, Viale Pieraccini 17, 50139, Firenze, Italy

    Lorenzo Antonuzzo

  7. Scienze Mediche e Chirurgiche, Azienda Ospedaliero-Universitaria, Policlinico Sant’Orsola-Malpighi, Bologna, Italy

    Davide Campana

  8. Oncologia Medica, Istituto Oncologico del Mediterraneo (IOM), Via Penninazzo 7, 95029, Viagrande, Italy

    Ivana Puliafito

  9. Anatomia Patologica, Azienda USL Romagna, Ospedale S. Maria delle Croci, Viale Randi 5, 48121, Ravenna, Italy

    Giulio Rossi

  10. Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Paradisa 2, 56126, Pisa, Italy

    Pinuccia Faviana

  11. Division of Human Pathology, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50139, Firenze, Italy

    Luca Messerini

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  1. Francesca Spada
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Correspondence to Nicola Fazio.

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Spada, F., Maisonneuve, P., Fumagalli, C. et al. Temozolomide alone or in combination with capecitabine in patients with advanced neuroendocrine neoplasms: an Italian multicenter real-world analysis. Endocrine 72, 268–278 (2021). https://doi.org/10.1007/s12020-020-02421-2

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